Dr Sanjay Sharma, founding director of the Cost-Effective Ocular Health Policy Unit at Queen's University in Ontario, Canada, announced this month at the annual American Academy of Ophthalmology meeting that prescribing high doses of vitamins to macular degeneration patients could save the health care system of North American over one and a half billion dollars over the next decade. Macular degeneration is a leading cause of blindness in older individuals. Recent studies have shown benefits for nutritional therapies in slowing down the progression of the disease.

Dr Sharma analyzed information obtained over the past seven years from national clinical trials and other studies to create a mathematical model to determine the value of various treatments for macular degeneration and their effects of the quality of patients' lives. He explained , "Our results demonstrate that the use of high-dose vitamin supplementation (vitamins C and E, plus beta carotene and zinc) by people suffering from age-related macular degeneration will result in both improved quality of life and reduced health care costs. We project that this strategy, if applied to those with the advanced 'dry' form of AMD over the coming decade could potentially save the North American health care system more than $1.5 billion. This would result from the anticipated reduction in demand for more expensive technologies used to treat the 'wet' form of AMD, which can progress from the dry form . . . The cost of drugs and medical services in Canada and the U.S. has gone up tremendously in the past decade. What we need is a rational system for deciding which drugs to cover under government-subsidized or private insurance plans. We're creating models to look at this, and at the value of these treatments for eye disease."

October 28, 2002

Calorie restriction keeps mice young at heart

Doctors Thomas Prolla and Richard Weindruch, and colleagues at the University of Wisconsin and University of Alabama, have utilized DNA microarrays to show that calorie restriction in mice inhibited age-related changes in gene expression by 19%. In research published in the October 28 2002 issue of Proceedings of the National Academy of Sciences, the researchers fed one group of mice a normal diet, and, starting at fourteen months of age, fed a second group 26% fewer calories than the control group. Examination of the heart was conducted at five months of age in some controls, and at thirty months of age for the remainder of the controls and the calorie restricted group.

Messenger RNA levels for 9,977 genes were obtained to determine their expression. Final analysis showed a 19% global inhibition of age-related gene expression changes in the restricted mice. Genes that were expressed in aging mice were those involved in structural roles, resulting in extracellular matrix protein deposition, fibrosis and heart muscle cell enlargement. Also observed was an increase in expression in genes involved in neurodegeneration. Additionally, there was a decrease in the expression of genes involved in lipid metabolism and fatty acid oxidation, which is the heart's major energy source, with a shift toward carbohydrate metabolism.

Calorie restriction also suppressed immune-related genes, which may be associated with less inflammation in the heart, enhanced DNA repair genes,and reduced genes inducing apoptosis. The authors were surprised to find that there was "no evidence that aging in the heart is associated with a transcriptional profile indicative of an oxidative stress response, as previously demonstrated for skeletal muscle and brain (of mice)". (Lee CK, et al, "Transcription profiles associated with aging and middle age-onset caloric restriction in mouse hearts", PNAS Oct 28 2002)

October 25, 2002

Vitamin supplements help HIV positive women gain weight in pregnancy

A study that will be published in the November 2002 issue of the American Journal of Clinical Nutrition has found that consumption of a multivitamin supplement by pregnant women who are HIV positive helped improve weight gain during pregnancy. HIV infection often leads to diminished appetite, nutrient malabsorption and opportunistic infections with consequent weight loss, which has adverse effects on offspring when occurring during pregnancy, such as low birth weight or prematurity.

Nine hundred and fifty-seven pregnant women in Tanzania who were HIV-positive were enrolled in the study. The women were between 12 and 27 weeks of gestation with an average age of 25, and an average weight of 125 pounds at enrollment. The researchers divided the participants into groups receiving an orally administered multivitamin supplement, a multivitamin supplement that did not include vitamin A, vitamin A alone or a placebo. The multivitamin contained vitamins A, B1, B2, B3, B6, B12, C and E, folic acid and beta-carotene. Participants also received separate supplements containing iron and folate.

The women were followed to the end of their pregnancies. It was found that during the third trimester, average weight gain was significantly higher and risk of low rate of weight gain lower for the women who received the multivitamins compared to the group receiving the placebo. When administered alone, vitamin A supplements did not effect overall or third trimester weight gain, but the vitamin was positively associated with weight during the second trimester when combined with multivitamins.

The authors, from the Harvard School of Public Health in Boston and Muhimbili University College of Health Science in Dar es Salaam, Tanzania, write that multivitamins may slow the progression of HIV or reduce the incidence and severity of secondary infections, thereby preventing weight loss.

October 23, 2002

Little worm offers big lessons

The October 24 2002 issue of the journal Nature published findings from researchers at Rutgers University, The State University of New Jersey, and the Albert Einstein College of Medicine, on the roundworm known Caenorhabditis elegans, which showed that an enzyme controlling muscle tissue loss, or sarcopenia, may play a role in the aging of the entire organism. Sarcopenia is a condition that occurs in humans as we get older, which is characterized by a loss of muscle mass and strength. By observing the aging process in roundworms, the researchers were surprised to find that the condition occurred in the worms as well.

Although it had been previously discovered that worms live longer who lack an enzyme called ape-1/P13 kinase, the current study found that this enzyme had to be present for sarcopenia to occur. The research suggests that the decline of one tissue type may direct the aging of the whole organism.

Principle investigator and associate professor in Rutgers' department of molecular biology and biochemistry, Monica Driscoll, commented, "Once you have figured out what a key molecule is doing in the worm, you can look for it in humans and expect the same things to happen. All the basic machinery is there, and the way things work in the worm is the way things work in people, though we are a bit more complicated with a few more bells and whistles. Ultimately, we would like to be in a position to engineer or adjust the chemistry of the body so that you can extend the period of health and delay some of the unwanted aspects of aging. The long-term goal is to regulate the responsible biochemical pathway through drug therapy. In this way, we could maintain the health of the muscle based on the lessons the little worm taught us."

October 21, 2002

Vitamin C and glutathione reduce age-related oxidative stress in rats

Oxygen-based free radical damage has been implicated in aging and age related diseases, and is itself generated by the neurodegenerative processes of aging according to one proposed theory. In a study published in the September-October 2002 issue of Annals of Nutrition & Metabolism, Dr M A Amer, of Mansoura University in Mansoura, Egypt, has found that providing the antioxidant nutrients vitamin C and glutathione to older rats significantly lowers oxidative stress compared to rats who did not receive the protective nutrients.

The eighteen-month-old rats were divided into groups receiving 100 milligrams per kilogram body weight glutathione and 30 milligrams per kilogram ascorbic acid daily for six weeks, or a control group who did not receive the nutrients. At study's conclusion, thiobarbituric acid reactive substances (TBARS) in the liver and testes were measured to determine lipid peroxidation. Serum levels of testosterone, thyroid hormones, cholesterol, triglycerides, copper and zinc were also measured. The rats who received glutathione and vitamin C were found to have higher levels in their testes, and significantly lower TBARS in both testes and liver than the controls. While thyroid hormones were not affected by antioxidant supplementation, testosterone levels significantly increased in the treated older rats, and cholesterol and triglycerides fell dramatically. Zinc and copper were found to have increased in serum and in the brain and testes.

Dr Amer speculates that vitamin C's benefit in the study could be due to its ability to help regenerate glutathione and activate antioxidant recycling pathways. The elevation of testosterone seen in the supplemented animals may be attributable to the lower levels of oxidative stress found in the testes and the elevation of glutathione observed in this group.

October 18, 2002

JAMA study shows folate may protect against miscarriage

A study conducted by researchers at the Karolinska Institutet in Sweden and researchers from the National Institute of Child Health and Human Development in the U.S. has concluded that folate deficiency is associated with an increased risk of early miscarriage. The study, published in the October 16 2002 issue of the Journal of the American Medical Association, was conducted between 1996 and 1998, and compared the plasma folate status of 468 women who had undergone spontaneous abortion at six to twelve weeks gestation with 921 women who were at the same stage of their pregnancies. The researchers recruited Swedish women for the study, because the lack of food fortification with folic acid in this country makes folate deficiency more prevalent, enabling them to better examine the relationship between folate deficiency and miscarriage. Fortification of grain products with folic acid was mandated in 1998 by the U.S. Food and Drug Administration to reduce the prevalence of neural tube defects in newborns.

Participants were queried on reproductive and health histories, and provided blood samples that were tested for folate levels. The researchers found that having adequate folate, defined as plasma levels between 5 and 8.9 nanomoles per liter, were associated with a 50% lower risk of miscarriage. While having adequate folate levels was protective against miscarriage, having high levels conferred no additional benefit.

National Institute of Child Health and Human Development director, Duane Alexander MD, stated, "The results of this study reinforce the importance of folate for women in their childbearing years. Not only does taking folic acid before conception prevent the devastating form of birth defects known as neural tube defects, but it also appears to lower the risk of early miscarriage."

October 16, 2002

Fish oil causes cancer cell suicide

Research conducted at the Institute for Nutrition Research at the University of Oslo, in Norway, presented this month by Hilde Heimli, shows that the fatty acids from fish oil and fatty fish is capable of destroying the mitochondria of certain cancer cells, leading to cell suicide. Mitochondria are the power plants of cells, located outside of the cell nucleus. These are the conclusions in a new thesis that Hilde Heimli at the presented in October 2002. The research was supported by the Norwegian Cancer Society.

Heimli showed that polyunsaturated omega-3 fatty acids are ingested by various leukemia and lymphoma cells in vitro, leading to apoptosis, or programmed cell death. For this to be accomplished, the cancer cells must contain an enzyme that activates the fatty acids. Cancer cells lacking adequate amounts of the enzyme do not react to the omega-3's.

Heimli believes there is no reason the process would not occur in vivo as well. She stated, "The experiments have been done in dishes in a laboratory setting. The polyunsaturated fatty acids that are used are eicosapentaenoic acid (EPA),which are the same type as found in fatty fish or regular fish oil capsules. The fatty acids are added to the the food given to the cancer cells in a way that is most like the body's own process."

She added, "Polyunsaturated fatty acids from fish also can initiate a less regulated cell death called necrosis. The reason for the necrotic cell death is an increased production of reactive oxygen species in the cells. It is possible to appose this necrosis by the presence of antioxidants such as Vitamin C and E."

October 14, 2002

First study of its kind shows coenzyme Q10 slows Parkinson's disease

The October 15 2002 issue of the American Medical Association journal Archives of Neurology, revealed the results of the Parkinson Study Group national clinical trial conducted at ten centers across the United States that showed that high doses of coenzyme Q10 can slow the deterioration that occurs with Parkinson's disease up to 44%. Coenzyme Q10 is a compound that exists in the power plants of every cell called mitochondria. Previous research has demonstrated that mitochondrial function is impaired in Parkinson's disease.

The researchers administered vitamin E or a 300, 600 or 1200 milligram daily dose of coenzyme Q10 combined with vitamin E to a group of 80 subjects with early Parkinson's disease who had not yet initiated the standard therapy of levodopa. Although levodopa can help alleviate symptoms of the disease, it does not slow its progression. Prior to and over the course of the study, participants were evaluated for motor skills, mental function, mood, and ability to perform activities of daily living, and were rated according to test scores. Subjects remained in the study until they needed medication for up to sixteen months, upon which time they were re-evaluated.

Half way through the study, the patients receiving 300 or 600 milligrams of coenzyme Q10 had better test scores than the placebo group, while the group receiving 1200 milligrams per day had significantly better scores, experiencing 44% less decline. This pattern continued until the end of the study.

Investigator and University of California San Diego professor of neurosciences, Richard Haas, MD, commented, "Recently, several rare mitochondrial diseases affecting younger people resulting from coenzyme Q10 deficiency have been described. These patients may respond dramatically to coenzyme Q10 treatment. Tissue coenzyme Q10 levels fall with aging and we do not know why this occurs. The normal lower levels of coenzyme Q10 in older individuals may be a contributing factor in the progression of some diseases of aging."

October 11, 2002

Vitamin D and genistein synergistically inhibit prostate cell growth

A study published in the October 2002 issue of Journal of Nutrition (www.nutrition.org) has shown that the growth of prostate epithelial cells in vitro is slowed by the soy isoflavone genistein as well as the hormonally active form of vitamin D, 1-alpha,25-dihydroxycholecalciferol, and that both compounds together produce a greater result than either of them produce separately. The same effect was observed with genistein and 25-hydroxycholecalciferol, a low calcemic vitamin D compound.

Researchers from Wake Forest University School of Medicine, in Winston-Salem, North Carolina, cultured two benign and one malignant prostate cell line and inoculated them with genistein and vitamin D in varying combinations and concentrations. Bar graphs of the results present a very clear picture of the least amount of cell growth occurring with the combination of the highest concentrations of genistein and 1-alpha,25-dihydroxycholecalciferol. They then tested the form of vitamin D known as 25-hydroxycholecalciferol, or 25-OHD3, alone or in varying combinations with genistein on nonmalignant cells, and again found the greatest inhibitory effect on cell growth occurred when the higher concentrations of both compounds were administered in combination.

Benign cells showed greater sensitivity to genistein than the malignant cells, and the response of the malignant cells to a genistein-vitamin D combination, while significant, was not as robust as the response elicited by nonmalignant cells. The researchers found that the combination blocked two phases of cell cycle growth in benign cells but only one phase in the prostate cancer cells.

These studies are the first to show synergism between genistein and vitamin D compounds in inhibiting prostate cell growth. The authors write, "Our data support the use of a combination of these two agents for both prevention and treatment of prostate cancer." (Rao A, Woodruff RD, Wade WN et al, "Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth", J Nutr 132:3191-3194.)

October 09, 2002

Curcumin protects against radiation damage

Researchers at the University of Rochester Medical Center have discovered protective benefits for the herb curcumin,against the radiation received by cancer patients. The pilot study results were presented at 44th annual meeting of the American Society for Therapeutic Radiology and Oncology on October 7, in New Orleans. Radiation therapy, while helpful in combating cancer, often causes burns and blisters in the patients who receive it.

The researchers, led by assistant professor of radiation oncology Ivan Ding, MD, gave two hundred mice 50 to 200 milligrams per kilogram oral curcumin per day, for five days before or five days after radiation, or both ( ten days). In another experiment, the researchers administered curcumin for four days prior and three days following radiation. Control groups of mice received no curcumin. When skin damage was assessed twenty days later, all of the mice who received curcumin had minimal skin damage.

Research team leader and chief of radiation oncology at the University of Rochester James P Wilmot Cancer Center, Paul Okunieff, MD, commented, "This is significant because skin damage is a real problem for patients undergoing radiation to treat their tumors. If a nontoxic, natural substance can help prevent this damage and enhance the effectiveness of our radiation, that's a winning situation... Nearly all cancer patients who get radiation treatment experience some form of skin damage - from mild sunburn all the way to blisters - that is painful for many. If we can find a simple way to help prevent that, it would make treatment a bit easier."

Curcumin, by its antiangiogentic property, is already known to be helpful in suppressing tumor growth. The authors advise further studies, but suggest that patients receiving radiation consider eating foods spiced with curry, which contains curcumin. They also stress that the curcumin in the study was given orally or intraperitoneally, and that applying curcumin topically would not be advised.

October 07, 2002

Government report proves what we knew: SAMe as effective as prescription drugs

An Evidence Report Summary prepared by the Rand Corporation and sponsored by the U.S. Department of Health and Human Services' Agency for Healthcare Research and Quality shows that S-adenosylmethionine, or SAMe is as effective as prescription drugs for osteoarthritis and depression, as well as some liver conditions. SAMe is found in every cell of the body and is currently taken as a nutritional supplement by many individuals. The report is the result of a three year effort of a team of sixteen medical professionals who reviewed 102 clinical trials of SAMe in order to determine its efficacy.

Examination of 14 studies on SAMe and osteoarthritis led to the conclusion that SAMe is as effective as nonsteroidal antiinflammatory drugs in the treatment of osteoarthritis. When 47 studies on SAMe and depression were analyzed, the panel concluded that SAMe was not associated with a significant difference in outcome compared to conventional antidepressants. And analysis of over 40 studies on SAMe and liver disease showed a benefit in cholestasis of pregnancy, caused by elevated levels of bilirubin in the liver.

UCLA assistant professor Hyla Cass, MD, commented, "The Department of Health and Human Services hired an impeccable group of researchers to examine 102 clinical studies to determine whether or not SAM-e works . . . their results are quite compelling. These new findings suggest that SAM-e works as effectively as prescription drugs and it does it without the side effects. This is big news for patients who suffer side effects from prescription antidepressants such as headaches, weight gain and the most significant - sexual dysfunction."

The Evidence Report summary on SAMe is published online at the Health and Human Services' website at www.ahrq.gov/clinic/epcsums/samesum.htm The full report will be available online later this year.

October 04, 2002

Antioxidant supplementation, exercise, up flu vaccine protection

The September 2002 issue of the Journal of Gerontology: Medical Sciences published an article and editorial that revealed an increased immune response to influenza immunization when older individuals were given a nutritional drink that was high in antioxidants. Flu vaccines provide protection against the disease in only half of the older people who receive them. The same issue of Journal of Gerontology contained the results of an additional study showing that exercise improves flu vaccine response as well.

The first study recruited nineteen participants aged sixty-five and older, who were given a drink containing calories, vitamins, minerals and enhanced antioxidants or a placebo for seven months. Before receiving the influenza vaccine and one month after, the subjects' antibody titers to three strains of flu were measured. A significant increase in antibody response to one of the strains was observed in the group receiving the supplemented drink, compared to those receiving the placebo.

In the second study, researchers at Iowa State university divided participants aged sixty-two and older into groups receiving either active, moderately active or sedentary levels of exercise before being immunized for influenza. When measured two weeks following immunization, anti-influenza IgG and IgM were found to be higher in the active group than in the moderately active or sedentary groups. It was also found that daily multivitamin intake was significantly correlated with interleukin-2 levels.

Because influenza can be particularly deadly to older persons, improving exercise levels and diet would be advisable to enhance immunity, as well as provide all of the other known benefits. Dr Marian L Kohut of Iowa State University in Ames, Iowa, who coauthored the exercise study, stressed that in order to be effective exercise must be "three or more times per week for twenty minutes or more at an intensity vigorous enough to work up a sweat."

October 02, 2002

Synthetic antioxidant blocks stroke damage

In a study published in the October 2002 issue of Free Radical Biology and Medicine, researchers from Duke University Medical Center, and National Jewish Medical Center in Denver, have shown that the synthetic antioxidant AEOL 10150 can help prevent tissue damage following strokes induced in rodents. The researchers tested the compound on rats that had undergone middle cerebral artery occlusion to induce ischemia for ninety minutes. An hour and a half following restoration of circulation, AEOL 10150 or a placebo were given intracerebroventricularly. AEOL 10150 reduced the area of tissue damage by 35% compared to controls and also reduced neurologic deficit. When the compound was given six hours after ninety minutes of middle cerebral artery occlusion, evaluation one week later showed that infarct size was reduced by 43%.

In another experiment, AEOL 10150 was given intravenously to mice in whom stroke was induced and reductions in infarct size (25%) and neurologic deficit were seen as well, showing that the compound crossed the blood-brain barrier. And in brain cell cultures deprived of oxygen and glucose for two hours, AEOL 10150 modified the levels of cellular compounds to concentrations consistent with those found to have a neuroprotective effect. It was further discovered that the compound affects inflammatory gene expression.

AEOL 10150 is a metalloporphyrin catalytic antioxidant that mimics superoxide dismutase, one of the body's own antioxidants. The compound was developed by study coauthor and Chairman of the Department of Medicine at National Jewish, James Crapo MD. Dr Crapo summarized, "Because the onset of a stroke can be difficult to detect, many patients do not get treatment for several hours. Our findings suggest that the antioxidant is a promising candidate for stroke therapy because it can prevent damage so many hours after the stroke begins."

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